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Human Proopiomelanocortin-(79–96), a Proposed Androgen Stimulatory Hormone, Does not Affect Steroidogenesis in Cultured Human Fetal Adrenal Cells^*

Department of Obstetrics, Gynecology, and Reproductive Sciences (S.H.M), the Metabolic Research Unit (S.H.M., W.L.M.), and the Department of Pediatrics (W.L.M.), University of California San Francisco, California 94143
the Division of Immunology, Beckman Research Institute of The City of Hope (J.E.S.) Duarte, California 91010

Address all correspondence and requests for reprints to: Walter L. Miller, M.D., Building MR IV, Room 209, University of California, San Francisco, California 94143–0978.

Whether the production of human adrenal androgens is stimulated by a hormone other than ACTH or angiotensin-II has long been controversial. A candidate for such a cortical androgen stimulatory hormone (CASH) is the proximal 18-amino acid hinge region of proopiomelanocortin (POMC). This region of POMC lies to the amino-terminal side of the ACTH region, displays considerable amino acid sequence variation among mammals, and has been reported to stimulate the secretion of dehydroepiandrosterone (DHEA) from cultured adult adrenal cells. We cultured human fetal adrenal cells with 10^–8 M CASH-18,10^–13 M ACTH, 10^–8 M CASH-18 plus 10^–13 M ACTH, 10^–8 M ACTH, or vehicle alone. Culture media were assayed for cortisol, DHEA, and DHEA sulfate, and cellular RNA was assayed for P450scc and P450cl7 mRNAs. ACTH (10^–8 M) increased steroid secretion and the mRNAs for P450scc and P450cl7, but the other treatments were indistinguishable from the control. Thus, CASH-18 does not affect steroidogenesis in primary cultures of human fetal adrenal cells. These data could be consistent with a model in which adrenarche, the onset of adrenal androgen synthesis at 8-10 yr of age, is mediated by developmentally programmed synthesis of a receptor for CASH. Alternatively, they are also consistent with this region of POMC having no CASH activity.

^* This work was supported by NIH Grants HD-22013 (to S.H.M.), HD-14900 (to J.E.S.), and DK-37922 and DK-42154 (to W.L.M.), support from the W. M. Heck Foundation (to S.H.M.), and NIH Grants HD-11979 for the Reproductive Endocrinology Center Core Facilities and HD-02335 for the Pediatric Endocrine Research Laboratory.

Received July 17, 1990.

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